Regulated gene expression is essential for a proper progression through the cell cycle. The transcription factor NF-Y has a fundamental function in transcriptional regulation of cell cycle genes, particularly of G2/M genes. In order to investigate common and distinct functions of NF-Y subunits in cell cycle regulation, NF-YA, NF-YB and NF-YC have been silenced by shRNAs in HCT116 cells. NF-YA loss led to a delay in S-phase progression, DNA damage and apoptosis: we showed the activation of the replication checkpoint, through the recruitment of Δp53 and of the replication proteins PCNA and Mcm7 to chromatin. Differently, NF-YB depletion impaired cells from exiting G2/M, but did not interfere with S-phase progression. Gene expression analysis of NF-YA and NF-YB inactivated cells highlighted a common set of hit genes, as well as a plethora of uncommon genes, unveiling a different effect of NF-Y subunits loss on NF-Y binding to its target genes. Chromatin extracts and ChIP analysis showed that NF-YA depletion was more effective than NF-YB in hitting NF-Y recruitment to CCAAT-promoters. Our data suggest a critical role of NF-Y expression, highlighting that the lack of the single subunits are differently perceived by the cells, which activate diverse cell cycle blocks and signaling pathways.
Specific inhibition of NF-Y subunits triggers different cell proliferation defects / P. Benatti, D. Dolfini, A. Viganò, M. Ravo, A. Weisz, C. Imbriano. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 39:13(2011 Jul), pp. 5356-5368.
|Titolo:||Specific inhibition of NF-Y subunits triggers different cell proliferation defects|
|Parole Chiave:||Protein Subunits ; Tumor Suppressor Protein p53; Gene Silencing ; DNA Damage ; Humans ; Gene Expression ; S Phase ; Cell Line, Tumor ; CCAAT-Binding Factor ; Cell Proliferation ; Cell Cycle ; DNA Replication|
|Settore Scientifico Disciplinare:||Settore BIO/18 - Genetica|
Settore BIO/11 - Biologia Molecolare
|Data di pubblicazione:||lug-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/nar/gkr128|
|Appare nelle tipologie:||01 - Articolo su periodico|